In 2013, American Society of Plastic Surgeons members placed 68,607 tissue expanders for breast reconstruction alone. While tissue expansion, the process of stretching skin in order to increase growth, has been utilized successfully for many years, complication rates remain high, particularly in areas with minimal recruitable normal skin such as the head, neck and extremities. One of the inherent problems with tissue expansion is that both the molecular events and the skin mechanical changes that occur in response to skin stretch are incompletely understood. While cellular studies have elucidated some mechanotransduction pathways in keratinocytes and fibroblasts, the actual mechanism of tissue growth in response to stretch involves complex interactions that cannot be replicated in cells alone. Furthermore, the ratios of skin growth in response to stretch have not been determined. In order to fully elucidate these data, an in vivo model that allows both biomechanical and biologic evaluation is required. We hypothesize that skin growth varies and is maximal in areas of maximum stretch, and this will be correlated with gene expression and activation of known mechanotransduction pathways. Our established minipig model of tissue expansion is a collaborative, multidisciplinary effort with Stanford Engineering and the University of Wisconsin--? Milwaukee that utilizes computerized 3D analysis to allow the precise calculation of the stretch and surface area growth of any point of skin of the animal. We will implant tissue expanders at two sites in four minipigs, and each expander will be filled at different times. Harvest of this stretched skin will facilitate tissue growth calculations, as wellas histologic, immunohistochemically, and gene expression analysis. These data will be correlated to stretch to elucidate a timeline of the biomechanical and molecular response to deformational force. We expect that these experiments will allow us to determine skin's growth response to stretch, as well as to determine the timeline of molecular events that are altered in association with this growth. These data will be utilized for further studies to determine the inherent changes in these pathways in irradiated tissues, and will also offer immediate clinical information to optimize current techniques in tissue expansion, particularly in areas where like donor tissue is highly limited, such as the head, neck, and extremities.